High Doses of Cocaine Cause Mouse Brain Cells to Eat Themselves

"Out-of-control autophagy."

FIONA MACDONALD

20 JAN 2016

Research in mice has shown that high doses of cocaine can trigger "out-of-control autophagy" in the brain - which means that the drug causes brain cells to literally digest themselves at an unprecedented rate. And that's not great news, considering around 1.9 million people in the US admit to regularly taking cocaine.

Although it sounds scary, autophagy is actually a totally normal way for our cells clean up their waste and stay healthy. But when mice are given a hefty dose of cocaine, that process goes dangerously into overdrive, a team from the Johns Hopkins University School of Medicine has discovered.

"A cell is like a household that is constantly generating trash," said lead author of the study, Prasun Guha. "Autophagy is the housekeeper that takes out the trash - it's usually a good thing. But cocaine makes the housekeeper throw away really important things, like mitochondria, which produce energy for the cell."

So why were the researchers so interested in how cocaine affects the brain? It's been known for years that cocaine can trigger cell death, but until now, no one has been able to confirm how this happens, and - more importantly - how to stop it.

There are three different ways that cells can commit suicide, but after examining neurons taken from mice that had been given cocaine, the team was able to clearly determine that the cells were dying as a result of out-of-control autophagy.

"We performed 'autopsies' to find out how cells die from high doses of cocaine," said one of the researchers, Solomon Snyder. "That information gave us immediate insight into how we might use a known compound to interfere with that process and prevent the damage."

The known compound he's talking about is called CGP3466B. It's an experimental drug that's been used in clinical trials against Parkinson's and motor neurone disease, so it's known to be safe in humans.

The researchers have now also shown that the compound can protect mouse neurons from being destroyed by cocaine use.

Unfortunately, just because CGP3466B protects mouse brain cells against the drug, doesn't mean it'll work in humans, and the researchers stress that we're a long way being able to protect our brains against the damage of cocaine.

But it's a good place to start. "Since cocaine works exclusively to modulate autophagy versus other cell death programs, there's a better chance that we can develop new targeted therapeutics to suppress its toxicity," said one of the team, Maged M. Harraz.

Some people might argue that there's no point in protecting people against the effects of cocaine when they're choosing to take it. But the research, which has been published in the Proceedings of the National Academy of Sciences, also found signs of out-of-control autophagy in mouse pups after their mothers had been given the drug - making it clear that it's not just users who are at risk.